RRC ID 82103
Author Kitao K, Nakagawa S, Miyazawa T.
Title An ancient retroviral RNA element hidden in mammalian genomes and its involvement in co-opted retroviral gene regulation.
Journal Retrovirology
Abstract BACKGROUND:Retroviruses utilize multiple unique RNA elements to control RNA processing and translation. However, it is unclear what functional RNA elements are present in endogenous retroviruses (ERVs). Gene co-option from ERVs sometimes entails the conservation of viral cis-elements required for gene expression, which might reveal the RNA regulation in ERVs.
RESULTS:Here, we characterized an RNA element found in ERVs consisting of three specific sequence motifs, called SPRE. The SPRE-like elements were found in different ERV families but not in any exogenous viral sequences examined. We observed more than a thousand of copies of the SPRE-like elements in several mammalian genomes; in human and marmoset genomes, they overlapped with lineage-specific ERVs. SPRE was originally found in human syncytin-1 and syncytin-2. Indeed, several mammalian syncytin genes: mac-syncytin-3 of macaque, syncytin-Ten1 of tenrec, and syncytin-Car1 of Carnivora, contained the SPRE-like elements. A reporter assay revealed that the enhancement of gene expression by SPRE depended on the reporter genes. Mutation of SPRE impaired the wild-type syncytin-2 expression while the same mutation did not affect codon-optimized syncytin-2, suggesting that SPRE activity depends on the coding sequence.
CONCLUSIONS:These results indicate multiple independent invasions of various mammalian genomes by retroviruses harboring SPRE-like elements. Functional SPRE-like elements are found in several syncytin genes derived from these retroviruses. This element may facilitate the expression of viral genes, which were suppressed due to inefficient codon frequency or repressive elements within the coding sequences. These findings provide new insights into the long-term evolution of RNA elements and molecular mechanisms of gene expression in retroviruses.
Volume 18(1)
Pages 36
Published 2021-11-10
DOI 10.1186/s12977-021-00580-2
PII 10.1186/s12977-021-00580-2
PMID 34753509
PMC PMC8579622
MeSH Animals Callithrix / genetics Callithrix / virology Endogenous Retroviruses / classification Endogenous Retroviruses / genetics* Endogenous Retroviruses / isolation & purification Evolution, Molecular Gene Expression Regulation, Viral* Gene Products, env / chemistry Gene Products, env / genetics Genome Humans Macaca / genetics Macaca / virology Mammals / genetics* Mammals / virology* Pregnancy Proteins / chemistry Pregnancy Proteins / genetics RNA, Viral / chemistry RNA, Viral / genetics*
Resource
Human and Animal Cells 293T(RCB2202) NIH3T3-3-4(RCB1862)